Formulation of Advanced or Complex Medicines 3

Question 1

What are colligative properties?

Answer 1

Properties of solutions that depend on the number of molecules in a given volume of solvent and not on the properties (e.g. size or mass) of the molecules

Question 2

What two types of solute concentrations are there?

Answer 2

Osmotic
Tonicity

Question 3

What happens when two solutions (of different concentrations) are separated by a semi-permeable membrane?

Answer 3

The solvent of solution will move from the low concentration to the high concentration

Question 4

What is the driving force of osmosis?

Answer 4

Osmotic pressure

Question 5

What happens when two solutions (of the same concentration) are separated by a semi-permeable membrane?

Answer 5

No movement of molecules
- they are iso-osmotic

Question 6

What is the difference between iso-osmotic and isotonic?

Answer 6

Isotonic solutions contain only non-penetrating solutes whereas isosmotic solutions contain both penetrating as well as non-penetrating solutes

Question 7

What is an isotonic solution?

Answer 7

A solution which causes a cell to neither lose or gain water

Question 8

What is a hypertonic solution?

Answer 8

A solution which causes a cell to lose water
- cell shrinks and becomes crenated
- reversible process

Question 9

What is a hypotonic solution?

Answer 9

A solution which causes a cell to gain water
- cell swells and ruptures
- irreversible process
- cytolysis
- osmotic lysis

Question 10

What considerations need to be made for different routes of administration regarding isotonicity?

Answer 10

Intrathecal
- yes
- must be made isotonic
Intravenous
- less than 15 ml
- no
- more than 15 ml
- yes
Intramuscular
- yes
- aids dispersion of drug into surrounding tissue
Subcutaneous
- no

Question 11

What is osmolality?

Answer 11

Concentration of solution expressed as moles of solute particles per kilogram of water

Question 12

What is osmolarity?

Answer 12

Concentration of solution expressed as moles of solute particles per litre of water

Question 13

What are the four calculations that can be used to adjust isotonicity?

Answer 13

Freezing point depression
Sodium chloride equivalents
Molar concentrations of ingredients
Serum osmolarity

Question 14

How is osmolarity calculated?

Answer 14

mOsmol/L = (g/L of solute)/(mol weight of solution)) x 1000 x no of ions

Question 15

What is the calculation for freezing point depression?

Answer 15

W = (0.52 - a) / b

Question 16

Where can you find pre-formulation information?

Answer 16

Pharmacopoeias
- general monographs
- specific product monographs
- specific drug monographs
Literature
- drug information
- stability
- uses
- methods of manufacture
- drug handbooks

Question 17

What pre-formulation issues need to overcome?

Answer 17

pH adjustment
Oxidation
Solubilising agents
Suspending agents
Osmotic activity
Isotonicity
Preseveratives

Question 18

Why does pH need to be adjusted?

Answer 18

Effect on solubility and stability of the active medicament

Question 19

What is the ideal pH of parenteral products?

Answer 19

pH 7.4 (blood)

Question 20

What are the consequences of parenteral products below pH 3?

Answer 20

Painful injection

Question 21

What are the consequences of parenteral products above pH 9?

Answer 21

Tissue necrosis

Question 22

Why can intravenous injections/infusions accept a wider pH range of products?

Answer 22

Blood buffers the effects

Question 23

Why is oxidation a problem in parenteral products?

Answer 23

Oxygen is a highly reactive species

Question 24

How does oxygen come into contact with parenteral products?

Answer 24

The container
- headspace of air

Question 25

What is purging?

Answer 25

Removing air from a container and replacing it with an inert gas e.g. nitrogen